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  • Articles  (44)
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  • 1
    Electronic Resource
    Electronic Resource
    Nicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus: a function mediated by a different nAChR than dopamine release from striatum (2001)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 76 (2001), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Acetylcholine release stimulated by nicotinic agonists was measured as radioactivity released from perfused synaptosomes prepared from mouse interpeduncular nucleus (IPN) that had been loaded with [3H]choline. Agonist-stimulated release was dependent upon external calcium and over 90% of released radioactivity was acetylcholine. The release process was characterized by dose response curves for 13 agonists and inhibition curves for six antagonists. α-Conotoxin MII did not inhibit this release, while α-conotoxin AuIB inhibited 50% of agonist-stimulated release. Comparison of this process with [3H]dopamine release from mouse striatal synaptosomes indicated that different forms of nicotinic acetylcholine receptors (nAChRs) may mediate these processes. This was confirmed by assays using mice homozygous for the β2 subunit null mutation. The deletion of the β2 subunit had no effect on agonist-stimulated acetylcholine release, but abolished agonist-stimulated release of dopamine from striatal synaptosomes. Mice heterozygous for the β2 subunit null mutation showed decreased dopamine release evoked by l-nicotine with no apparent change in EC50 value, as well as similar decreases in both transient and persistent phases of release with no changes in desensitization rates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2001.00019.x
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  • 2
    Electronic Resource
    Electronic Resource
    Imaging metalloproteinase activity in vivo (2001)
    [s.l.] : Nature Publishing Group
    Nature medicine 7 (2001), S. 655-656 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Cancer is one of the most feared diseases in modern society. Approximately 50% of cancer patients die because the initial tumor becomes metastatic, spreading beyond the site of origin. Studies have demonstrated a positive correlation between cancer progression and expression of extracellular ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/89016
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  • 3
    Electronic Resource
    Electronic Resource
    A matrix metalloproteinase expressed on the surface of invasive tumour cells (1994)
    [s.l.] : Nature Publishing Group
    Nature 370 (1994), S. 61-65 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] We screened cDNAs with homology to conserved regions in matrix metalloproteinase (MMP) genes (Fig. 1 legend) and iso-lated a unique 3.4-kilobase (kb) cDNA fragment (MMP-X1) from a human placenta cDNA library. This cDNA encodes a unique protein of 582 amino acids (Mr 66K) which can be closely ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/370061a0
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  • 4
    Electronic Resource
    Electronic Resource
    Mechanics of Leukocyte Deformation and Adhesion to Endothelium in Shear Flow (1999)
    Springer
    Annals of biomedical engineering 27 (1999), S. 298-312 
    Details
    ISSN: 1573-9686
    Keywords: In vivo ; Incipient cell rolling ; Transient contact ; Drag force ; Modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The mechanics of leukocyte [white blood cell (WBC)] deformation and adhesion to endothelial cells (EC) in shear flow has been investigated. Experimental data on transient WBC–EC adhesion were obtained from in vivo measurements. Microscopic images of WBC–EC contact during incipient WBC rolling revealed that for a given wall shear stress, the contact area increases with time as new bonds are formed at the leading edge, and then decreases with time as the trailing edge of the WBC membrane peels away from the EC. A two-dimensional model (2D) was developed consisting of an elastic ring adhered to a surface under fluid stresses. This ring represents an actin-rich WBC cortical layer and contains an incompressible fluid as the cell interior. All molecular bonds are modeled as elastic springs distributed in the WBC–EC contact region. Variations of the proportionality between wall shear stress (τ w ) in the vicinity of the WBC and the resulting drag force (F s ), i.e., Fs/τw, reveal its decrease with WBC deformation and increasing vessel channel height (2D). The computations also find that the peeling zone between adherent WBC and EC may account for less than 5% of the total contact interface. Computational studies describe the WBC–EC adhesion and the extent of WBC deformation during the adhesive process. © 1999 Biomedical Engineering Society. PAC99: 8717-d, 8719Tt, 8717Aa
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1114/1.143
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  • 5
    Electronic Resource
    Electronic Resource
    Particle Motion Within In Vitro Models of Stenosed Internal Carotid and Left Anterior Descending Coronary Arteries (1998)
    Springer
    Annals of biomedical engineering 26 (1998), S. 190-199 
    Details
    ISSN: 1573-9686
    Keywords: Particle residence time ; In vitro model ; Artery: carotid ; Artery: coronary ; Stenosis ; Particle motion ; Model ; Artery: stenosed
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Asymmetric 75% and 95% area reduction, transparent Sylgard stenotic models were operated under internal carotid artery (ICA) (Womersley parameter, α=5.36, Remean=213 and 180, respectively, and Repeak=734 and 410, respectively) and left anterior descending coronary artery (LAD) flow wave forms (α=2.65,Remean=59 and 57, respectively, and Repeak=137 and 94, respectively) to evaluate the effect of these conditions on particle residence times downstream of the stenoses. Amberlite particles (1.05 g/cm3, 400 μm) were added to the fluid to simulate platelets and their motion through the stenotic region and were traced using a laser light sheet flow visualization method with pseudo-color display. Two-dimensional (2D) particle motions were recorded and particle washout in the stenotic throat and downstream section were computed for all cases. All four model cases demonstrated jetting through the stenosis which followed an arching pattern around a large separation zone downstream. Considerable mixing was observed within these vortex regions during high flow phases. Particle washout profiles showed no clear trend between the degrees of stenosis although particles downstream of the stenoses tended to remain longer for LAD conditions. The critical washout cycle (1% of particles remaining downstream of the stenosis), however, was longer for the 95% stenoses cases under each flow condition due to the larger protected region immediately downstream and maximal for the LAD 95% case. Results of this study suggest that particle residence times downstream of 75% and 95% stenoses (~ 3–6 s for ICA and ~ 8–10 s for LAD) exceed the minimum time for platelet adhesion (~ 1 s) for at least 1% of cells and, thus, may be sufficient to initiate thrombus formation under resting conditions. © 1998 Biomedical Engineering Society. PAC98: 8745Hw, 8722-q, 4727Wg, 4732Cc
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1114/1.131
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  • 6
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    A multi-model CMIP6-PMIP4 study of Arctic sea ice at 127 ka: sea ice data compilation and model differences (2021)
    COPERNICUS GESELLSCHAFT MBH
    In:  EPIC3Climate of the Past, COPERNICUS GESELLSCHAFT MBH, 17(1), pp. 37-62, ISSN: 1814-9324
    Details
    Publication Date: 2021-06-07
    Description: The Last Interglacial period (LIG) is a period with increased summer insolation at high northern latitudes, which results in strong changes in the terrestrial and marine cryosphere. Understanding the mechanisms for this response via climate modelling and comparing the models' representation of climate reconstructions is one of the objectives set up by the Paleoclimate Modelling Intercomparison Project for its contribution to the sixth phase of the Coupled Model Intercomparison Project. Here we analyse the results from 16 climate models in terms of Arctic sea ice. The multi-model mean reduction in minimum sea ice area from the pre industrial period (PI) to the LIG reaches 50 % (multi-model mean LIG area is 3.20×106 km2, compared to 6.46×106 km2 for the PI). On the other hand, there is little change for the maximum sea ice area (which is 15–16×106 km2 for both the PI and the LIG. To evaluate the model results we synthesise LIG sea ice data from marine cores collected in the Arctic Ocean, Nordic Seas and northern North Atlantic. The reconstructions for the northern North Atlantic show year-round ice-free conditions, and most models yield results in agreement with these reconstructions. Model–data disagreement appear for the sites in the Nordic Seas close to Greenland and at the edge of the Arctic Ocean. The northernmost site with good chronology, for which a sea ice concentration larger than 75 % is reconstructed even in summer, discriminates those models which simulate too little sea ice. However, the remaining models appear to simulate too much sea ice over the two sites south of the northernmost one, for which the reconstructed sea ice cover is seasonal. Hence models either underestimate or overestimate sea ice cover for the LIG, and their bias does not appear to be related to their bias for the pre-industrial period. Drivers for the inter-model differences are different phasing of the up and down short-wave anomalies over the Arctic Ocean, which are associated with differences in model albedo; possible cloud property differences, in terms of optical depth; and LIG ocean circulation changes which occur for some, but not all, LIG simulations. Finally, we note that inter-comparisons between the LIG simulations and simulations for future climate with moderate (1 % yr−1) CO2 increase show a relationship between LIG sea ice and sea ice simulated under CO2 increase around the years of doubling CO2. The LIG may therefore yield insight into likely 21st century Arctic sea ice changes using these LIG simulations.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 7
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    Large-scale features of Last Interglacial climate: results from evaluating the lig127k simulations for the Coupled Model Intercomparison Project (CMIP6)–Paleoclimate Modeling Intercomparison Project (PMIP4) (2021)
    Copernicus
    In:  EPIC3Climate of the Past, Copernicus, 17(1), pp. 63-94, ISSN: 1814-9332
    Details
    Publication Date: 2021-07-01
    Description: The modeling of paleoclimate, using physically based tools, is increasingly seen as a strong out-of-sample test of the models that are used for the projection of future climate changes. New to the Coupled Model Intercomparison Project (CMIP6) is the Tier 1 Last Interglacial experiment for 127 000 years ago (lig127k), designed to address the climate responses to stronger orbital forcing than the midHolocene experiment, using the same state-of-the-art models as for the future and following a common experimental protocol. Here we present a first analysis of a multi-model ensemble of 17 climate models, all of which have completed the CMIP6 DECK (Diagnostic, Evaluation and Characterization of Klima) experiments. The equilibrium climate sensitivity (ECS) of these models varies from 1.8 to 5.6 ∘C. The seasonal character of the insolation anomalies results in strong summer warming over the Northern Hemisphere continents in the lig127k ensemble as compared to the CMIP6 piControl and much-reduced minimum sea ice in the Arctic. The multi-model results indicate enhanced summer monsoonal precipitation in the Northern Hemisphere and reductions in the Southern Hemisphere. These responses are greater in the lig127k than the CMIP6 midHolocene simulations as expected from the larger insolation anomalies at 127 than 6 ka. New synthesis for surface temperature and precipitation, targeted for 127 ka, have been developed for comparison to the multi-model ensemble. The lig127k model ensemble and data reconstructions are in good agreement for summer temperature anomalies over Canada, Scandinavia, and the North Atlantic and for precipitation over the Northern Hemisphere continents. The model–data comparisons and mismatches point to further study of the sensitivity of the simulations to uncertainties in the boundary conditions and of the uncertainties and sparse coverage in current proxy reconstructions. The CMIP6–Paleoclimate Modeling Intercomparison Project (PMIP4) lig127k simulations, in combination with the proxy record, improve our confidence in future projections of monsoons, surface temperature, and Arctic sea ice, thus providing a key target for model evaluation and optimization.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 8
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    The PMIP4 contribution to CMIP6 – Part 4: Scientific objectives and experimental design of the PMIP4-CMIP6 Last Glacial Maximum experiments and PMIP4 sensitivity experiments (2017)
    COPERNICUS GESELLSCHAFT MBH
    In:  EPIC3Geoscientific Model Development, COPERNICUS GESELLSCHAFT MBH, 10(11), pp. 4035-4055, ISSN: 1991-959X
    Details
    Publication Date: 2017-11-20
    Description: The Last Glacial Maximum (LGM, 21 000 years ago) is one of the suite of paleoclimate simulations included in the current phase of the Coupled Model Intercomparison Project (CMIP6). It is an interval when insolation was similar to the present, but global ice volume was at a maximum, eustatic sea level was at or close to a minimum, greenhouse gas concentrations were lower, atmospheric aerosol loadings were higher than today, and vegetation and land-surface characteristics were different from today. The LGM has been a focus for the Paleoclimate Modelling Intercomparison Project (PMIP) since its inception, and thus many of the problems that might be associated with simulating such a radically different climate are well documented. The LGM state provides an ideal case study for evaluating climate model performance because the changes in forcing and temperature between the LGM and pre-industrial are of the same order of magnitude as those projected for the end of the 21st century. Thus, the CMIP6 LGM experiment could provide additional information that can be used to constrain estimates of climate sensitivity. The design of the Tier 1 LGM experiment (lgm) includes an assessment of uncertainties in boundary conditions, in particular through the use of different reconstructions of the ice sheets and of the change in dust forcing. Additional (Tier 2) sensitivity experiments have been designed to quantify feedbacks associated with land-surface changes and aerosol loadings, and to isolate the role of individual forcings. Model analysis and evaluation will capitalize on the relative abundance of paleoenvironmental observations and quantitative climate reconstructions already available for the LGM.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 9
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    Agreement between reconstructed and modeled boreal precipitation of the Last Interglacial (2019)
    American Association for the Advancement of Science
    In:  EPIC3Science Advances, American Association for the Advancement of Science, 5(11), pp. eaax7047, ISSN: 2375-2548
    Details
    Publication Date: 2019-11-25
    Description: The last extended time period when climate may have been warmer than today was during the Last Interglacial (LIG; ca. 129 to 120 thousand years ago). However, a global view of LIG precipitation is lacking. Here, seven new LIG climate models are compared to the first global database of proxies for LIG precipitation. In this way, models are assessed in their ability to capture important hydroclimatic processes during a different climate. The models can reproduce the proxy-based positive precipitation anomalies from the preindustrial period over much of the boreal continents. Over the Southern Hemisphere, proxy-model agreement is partial. In models, LIG boreal monsoons have 42% wider area than in the preindustrial and produce 55% more precipitation and 50% more extreme precipitation. Austral monsoons are weaker. The mechanisms behind these changes are consistent with stronger summer radiative forcing over boreal high latitudes and with the associated higher temperatures during the LIG.
    Repository Name: EPIC Alfred Wegener Institut
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  • 10
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    Large-scale features and evaluation of the PMIP4-CMIP6 midHolocene simulations (2020)
    COPERNICUS GESELLSCHAFT MBH
    In:  EPIC3Climate of the Past, COPERNICUS GESELLSCHAFT MBH, 16(5), pp. 1847-1872, ISSN: 1814-9332
    Details
    Publication Date: 2021-08-25
    Description: The mid-Holocene (6000 years ago) is a standard time period for the evaluation of the simulated response of global climate models using palaeoclimate reconstructions. The latest mid-Holocene simulations are a palaeoclimate entry card for the Palaeoclimate Model Intercomparison Project (PMIP4) component of the current phase of the Coupled Model Intercomparison Project (CMIP6) – hereafter referred to as PMIP4-CMIP6. Here we provide an initial analysis and evaluation of the results of the experiment for the mid-Holocene. We show that state-of-the-art models produce climate changes that are broadly consistent with theory and observations, including increased summer warming of the Northern Hemisphere and associated shifts in tropical rainfall. Many features of the PMIP4-CMIP6 simulations were present in the previous generation (PMIP3-CMIP5) of simulations. The PMIP4-CMIP6 ensemble for the mid-Holocene has a global mean temperature change of −0.3 K, which is −0.2 K cooler than the PMIP3-CMIP5 simulations predominantly as a result of the prescription of realistic greenhouse gas concentrations in PMIP4-CMIP6. Biases in the magnitude and the sign of regional responses identified in PMIP3-CMIP5, such as the amplification of the northern African monsoon, precipitation changes over Europe, and simulated aridity in mid-Eurasia, are still present in the PMIP4-CMIP6 simulations. Despite these issues, PMIP4-CMIP6 and the mid-Holocene provide an opportunity both for quantitative evaluation and derivation of emergent constraints on the hydrological cycle, feedback strength, and potentially climate sensitivity.
    Repository Name: EPIC Alfred Wegener Institut
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